A number of pharmaceuticals are not stable against oxygen and water vapor. Therefore, most of the commercially available pharmaceuticals, especially pharmaceutical solid preparations, are packaged with a packaging material such as a PTP (press through pack) sheet and protected from oxygen and water vapor.
Meanwhile, at medical sites and dispensing pharmacies, to prevent patients from forgetting to take their prescribed drugs and making mistakes in the dosage thereof, it is widely practiced to use single-dose package prepared by taking out a plurality of pharmaceuticals to be taken at once from the respective packages of PTP sheet or the like and provide the pharmaceuticals altogether in one bag. Furthermore, in western countries, patients often remove their pharmaceuticals from the respective packages of PTP sheet or the like and place them in separate pill cases or the like for storage. Therefore, there has been a demand for a method of improving the water vapor barrier property and oxygen barrier property, that is, gas barrier properties, of a pharmaceutical solid preparation itself.
As a method of improving the gas barrier properties of a pharmaceutical solid preparation itself, methods of sugar-coating a pharmaceutical solid preparation and methods of film-coating with a polymeric substance have been put into practice. For instance, there have been developed a film coating agent in which stearic acid is blended with aminoalkyl methacrylate copolymer E (Eudragit EPO (registered trademark); Degussa Co.) (Japanese Translated PCT Patent Application Laid-open No. 2004-518750); a resin composition obtained by copolymerizing a polyvinyl alcohol with a polymerizable vinyl monomer (WO 2005/019286); a coating agent obtained by adding talc and a surfactant to a polyvinyl alcohol (JP 2006-188490 A); and a film coating agent in which bentonite is uniformly dispersed in the form of a certain structure in PVA (WO 2010/074223).
Furthermore, the needs for a gas barrier film coating against those substances other than oxygen and water vapor include the needs of preventing volatile (subliminal) drugs or their decomposition products from being spread. When such substances are spread, they may generate a bad odor and/or cause problems of, for example, color change of other drugs when combined in a single-dose formulation. For example, in olmesartan medoxomil preparations which are angiotensin II receptor antagonists, it is known that the (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl group released from olmesartan medoxomil is hydrolyzed into diacetyl to cause a diacetyl-originated odor. Further, olmesartan medoxomil preparations are also known to induce color change in a metformin hydrochloride preparation when placed in a single-dose package with a metformin hydrochloride preparation and stored under a high-temperature and high-humidity condition. This color change is caused by a reaction between diacetyl originated from olmesartan medoxomil and the guanidino group of metformin hydrochloride.
As a method improving such odor and color change problems, there have been reported a pharmaceutical package comprising a chemisorptive drying agent (WO 2008/041663), a film coating comprising carboxymethylcellulose (WO 2006/123765) and a coating comprising a polyvinyl alcohol copolymer (WO 2007/145191).
However, not only does it require a long time to sugar-coat a pharmaceutical solid preparation for the purpose of attaining gas barrier properties, but such sugar coating also has a large thickness and it thus enlarges the pharmaceutical solid preparation itself, so that it may impose a burden upon patients for taking such a large pharmaceutical solid preparation and may also extend the time required for the drug to take effect.
Moreover, among those conventional methods of film-coating a pharmaceutical solid preparation with a polymeric substance, only the film coating agent of WO '223 can attain excellent gas barrier properties equivalent to a PTP sheet (water vapor permeability: less than 1.0×10−4 g·mm/cm2·24 hr·atm, oxygen permeability coefficient: less than 1.0×10−4 cm3·mm/cm2·24 hr·atm) and those gas barrier properties that are obtained by other methods are not comparable to those of a PTP sheet.
Furthermore, with regard to the film coating agent of WO '223, since the disintegrating force of the resulting film itself is weak, it has been pointed out not only that a delay in disintegration may occur to affect the drug effect when the disintegration properties of a pharmaceutical solid preparation to be coated are not sufficient, but also that the bioequivalence test associated with formulation change may become more troublesome.
Therefore, it could be helpful to provide a coating agent for a pharmaceutical solid preparation which imparts an unpackaged pharmaceutical solid preparation with excellent barrier properties equivalent to those of a PTP sheet without affecting the disintegration properties of the pharmaceutical solid preparation.